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C2-ceramide enhances sorafenib-induced caspase-dependent apoptosis via PI3K/AKT/mTOR and Erk signaling pathways in HCC cells
by
Jiang, Shanshan
, Li, Jiyang
, An, Duopeng
, Peng, Yuzhe
, Wang, Qian
, Dong, Mengxue
, Guan, Zhongbin
, Kuerban, Kudelaidi
, Ye, Li
, Feng, Meiqing
in
1-Phosphatidylinositol 3-kinase
/ AKT protein
/ Antibodies
/ Apoptosis
/ Apoptosis - drug effects
/ Applied Genetics and Molecular Biotechnology
/ BAX protein
/ Bcl-2 protein
/ Biomedical and Life Sciences
/ Biotechnology
/ Cancer therapies
/ Cancer treatment
/ Carcinoma, Hepatocellular - metabolism
/ Caspase-3
/ Caspase-9
/ Cell adhesion & migration
/ Cell cycle
/ cell cycle checkpoints
/ Cell growth
/ Cell Line, Tumor
/ Cell migration
/ cell movement
/ Cell Survival - drug effects
/ Cell Survival - physiology
/ Cellular biology
/ Ceramide
/ ceramides
/ Combination therapy
/ Cytochrome
/ Cytochrome c
/ Depolarization
/ Drug therapy
/ Flow Cytometry
/ Growth factors
/ Hepatocellular carcinoma
/ hepatoma
/ Humans
/ Kinases
/ Life Sciences
/ Liver cancer
/ Medical research
/ Microbial Genetics and Genomics
/ Microbiology
/ mitochondria
/ neoplasm cells
/ Niacinamide - analogs & derivatives
/ Niacinamide - pharmacology
/ Pathogenesis
/ Phenylurea Compounds - pharmacology
/ Phosphatidylinositol 3-Kinases - genetics
/ Phosphatidylinositol 3-Kinases - metabolism
/ Prescription drugs
/ protein synthesis
/ Proteins
/ Proto-Oncogene Proteins c-akt - genetics
/ Proto-Oncogene Proteins c-akt - metabolism
/ Reactive oxygen species
/ Signal transduction
/ Sphingosine - analogs & derivatives
/ Sphingosine - pharmacology
/ Studies
/ therapeutics
/ TOR protein
/ TOR Serine-Threonine Kinases - genetics
/ TOR Serine-Threonine Kinases - metabolism
/ Tumor cells
/ Western blotting
2017
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C2-ceramide enhances sorafenib-induced caspase-dependent apoptosis via PI3K/AKT/mTOR and Erk signaling pathways in HCC cells
by
Jiang, Shanshan
, Li, Jiyang
, An, Duopeng
, Peng, Yuzhe
, Wang, Qian
, Dong, Mengxue
, Guan, Zhongbin
, Kuerban, Kudelaidi
, Ye, Li
, Feng, Meiqing
in
1-Phosphatidylinositol 3-kinase
/ AKT protein
/ Antibodies
/ Apoptosis
/ Apoptosis - drug effects
/ Applied Genetics and Molecular Biotechnology
/ BAX protein
/ Bcl-2 protein
/ Biomedical and Life Sciences
/ Biotechnology
/ Cancer therapies
/ Cancer treatment
/ Carcinoma, Hepatocellular - metabolism
/ Caspase-3
/ Caspase-9
/ Cell adhesion & migration
/ Cell cycle
/ cell cycle checkpoints
/ Cell growth
/ Cell Line, Tumor
/ Cell migration
/ cell movement
/ Cell Survival - drug effects
/ Cell Survival - physiology
/ Cellular biology
/ Ceramide
/ ceramides
/ Combination therapy
/ Cytochrome
/ Cytochrome c
/ Depolarization
/ Drug therapy
/ Flow Cytometry
/ Growth factors
/ Hepatocellular carcinoma
/ hepatoma
/ Humans
/ Kinases
/ Life Sciences
/ Liver cancer
/ Medical research
/ Microbial Genetics and Genomics
/ Microbiology
/ mitochondria
/ neoplasm cells
/ Niacinamide - analogs & derivatives
/ Niacinamide - pharmacology
/ Pathogenesis
/ Phenylurea Compounds - pharmacology
/ Phosphatidylinositol 3-Kinases - genetics
/ Phosphatidylinositol 3-Kinases - metabolism
/ Prescription drugs
/ protein synthesis
/ Proteins
/ Proto-Oncogene Proteins c-akt - genetics
/ Proto-Oncogene Proteins c-akt - metabolism
/ Reactive oxygen species
/ Signal transduction
/ Sphingosine - analogs & derivatives
/ Sphingosine - pharmacology
/ Studies
/ therapeutics
/ TOR protein
/ TOR Serine-Threonine Kinases - genetics
/ TOR Serine-Threonine Kinases - metabolism
/ Tumor cells
/ Western blotting
2017
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C2-ceramide enhances sorafenib-induced caspase-dependent apoptosis via PI3K/AKT/mTOR and Erk signaling pathways in HCC cells
by
Jiang, Shanshan
, Li, Jiyang
, An, Duopeng
, Peng, Yuzhe
, Wang, Qian
, Dong, Mengxue
, Guan, Zhongbin
, Kuerban, Kudelaidi
, Ye, Li
, Feng, Meiqing
in
1-Phosphatidylinositol 3-kinase
/ AKT protein
/ Antibodies
/ Apoptosis
/ Apoptosis - drug effects
/ Applied Genetics and Molecular Biotechnology
/ BAX protein
/ Bcl-2 protein
/ Biomedical and Life Sciences
/ Biotechnology
/ Cancer therapies
/ Cancer treatment
/ Carcinoma, Hepatocellular - metabolism
/ Caspase-3
/ Caspase-9
/ Cell adhesion & migration
/ Cell cycle
/ cell cycle checkpoints
/ Cell growth
/ Cell Line, Tumor
/ Cell migration
/ cell movement
/ Cell Survival - drug effects
/ Cell Survival - physiology
/ Cellular biology
/ Ceramide
/ ceramides
/ Combination therapy
/ Cytochrome
/ Cytochrome c
/ Depolarization
/ Drug therapy
/ Flow Cytometry
/ Growth factors
/ Hepatocellular carcinoma
/ hepatoma
/ Humans
/ Kinases
/ Life Sciences
/ Liver cancer
/ Medical research
/ Microbial Genetics and Genomics
/ Microbiology
/ mitochondria
/ neoplasm cells
/ Niacinamide - analogs & derivatives
/ Niacinamide - pharmacology
/ Pathogenesis
/ Phenylurea Compounds - pharmacology
/ Phosphatidylinositol 3-Kinases - genetics
/ Phosphatidylinositol 3-Kinases - metabolism
/ Prescription drugs
/ protein synthesis
/ Proteins
/ Proto-Oncogene Proteins c-akt - genetics
/ Proto-Oncogene Proteins c-akt - metabolism
/ Reactive oxygen species
/ Signal transduction
/ Sphingosine - analogs & derivatives
/ Sphingosine - pharmacology
/ Studies
/ therapeutics
/ TOR protein
/ TOR Serine-Threonine Kinases - genetics
/ TOR Serine-Threonine Kinases - metabolism
/ Tumor cells
/ Western blotting
2017
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C2-ceramide enhances sorafenib-induced caspase-dependent apoptosis via PI3K/AKT/mTOR and Erk signaling pathways in HCC cells
Journal Article
C2-ceramide enhances sorafenib-induced caspase-dependent apoptosis via PI3K/AKT/mTOR and Erk signaling pathways in HCC cells
2017
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Overview
Sorafenib as an effective multikinase inhibitor has been approved for the clinical treatment against advanced hepatocellular carcinoma (HCC). HCC treatment requires usually combined therapy because of its complex pathogenesis. Ceramide has been confirmed to induce remarkable apoptosis in human tumor cells and has attracted increasing attention in investigations on combination therapy. In this paper, the anti-HCC effect of sorafenib combined with C2-ceramide was investigated on cell vitality, apoptosis, and migration, and the underlying mechanism was examined using flow cytometry and western blot. Bel7402 cells coincubated with sorafenib and C2-ceramide exhibited lower cell vitality and more irregular cellular morphology and cell cycle arrest. Sorafenib plus C2-ceramide stimulated significantly the production of reactive oxygen species (ROS) and mitochondrial depolarization, which promoted caspases-dependent cell apoptosis as illustrated by related protein expression including caspase 3, caspase 9, Bax, Bcl-2, and cytochrome c. Combination treatment of sorafenib and C2-ceramide inhibited obviously cell growth and proliferation via PI3K/AKT/mTOR and Erk signaling pathways. Furthermore, the combination treatment was proved to inhibit cell migration and epithelial-mesenchymal transition (EMT). These findings indicated that the combination of C2-ceramide and sorafenib provided synergistic inhibitory effects on HCC cells.
Publisher
Springer Berlin Heidelberg,Springer,Springer Nature B.V
Subject
1-Phosphatidylinositol 3-kinase
/ Applied Genetics and Molecular Biotechnology
/ Biomedical and Life Sciences
/ Carcinoma, Hepatocellular - metabolism
/ Cell Survival - drug effects
/ Ceramide
/ hepatoma
/ Humans
/ Kinases
/ Microbial Genetics and Genomics
/ Niacinamide - analogs & derivatives
/ Phenylurea Compounds - pharmacology
/ Phosphatidylinositol 3-Kinases - genetics
/ Phosphatidylinositol 3-Kinases - metabolism
/ Proteins
/ Proto-Oncogene Proteins c-akt - genetics
/ Proto-Oncogene Proteins c-akt - metabolism
/ Sphingosine - analogs & derivatives
/ Studies
/ TOR Serine-Threonine Kinases - genetics
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